PubMed Health⌕ Search

Biomedical subjects

Masami Nagai

Publications and source records attributed to Masami Nagai.

At least 19 recordsLinked to original sources

Diagnostic accuracy of imprint cytology in the assessment of Hodgkin's disease in Japan.

Our objective was to evaluate the usefulness of cytomorphologic assessment in the accuracy of diagnosis of Hodgkin's disease (HD), using imprint cytological preparations over a 18-yr period. Imprint materials from 34 HD cases were reviewed using cytomorphological and immunocytochemical studies. Twenty-six cases (76.5%) were diagnosed to be HD and 6 cases (17.6%) were suspected to be HD, but 2 cases (5.9%) were cytologically diagnosed as reactive lesions, because of an insufficient number of Reed-Sternberg (RS) cells. The 6 suspected cases were definitively diagnosed as HD, using immunocytochemistry. Immunophenotyping of RS cells in 32 cases (excluding the two cases of reactive lesions) showed CD30+ in 31 (96.9%) cases, CD15+ in 22 (68.8%) cases and CD20+ in 12 (37.5%) cases. RS cells were immunophenotypically classified into five groups: A, (CD 30+, 15+, 20-) 15 (46.9%); B, (CD30+, 15-, 20-) 5 (15.6%); C, (CD 30+, 15+, 20+) 6 (18.8%); D, (CD30+, 15-, 20+) 5 (15.6%); and E, (CD30-, 15+, 20+) 1 (3.1%). Cytomorphologic differences in RS cells were identified between group D and other groups (CD15+ and/ or CD20-). The former had a low polymorphic shape (like popcorn), and the latter had a more classical polymorphic shape. Epstein-Barr virus (EBV)-latent membrane protein-1(LMP-1) was identified in 16 (50%) cases. LMP-1 expression was found not only in classic RS cells, but also in smaller variants. These variants did not match the morphologic criteria of RS cells, but expressed the common phenotype (CD30+, CD15+/-) of RS cells, suggesting the same cellular origin as RS cells. This study demonstrated that imprint cytology from lymph node biopsies can be a useful tool for the diagnosis and the evaluation of the cellular biology of HD.

Adolescent↗

A new polyclonal antibody that recognizes a human receptor for hyaluronan mediated motility.

The receptor for hyaluronan mediated motility (RHAMM), a hyaluronan (HA) binding protein, has been shown to play an important role in the motility and invasiveness of malignant cells. We have developed a polyclonal antibody against human RHAMM. A new polyclonal antibody was raised against a mixture of C-terminal RHAMM, which is capable of binding to HA, and the central domain. The antibody showed immunoreactivity to these two peptides, and detected a 95 kDa protein. Immunohistochemically, RHAMM detected by the antibody was present in the cytoplasm and nucleus of malignant B cells. Binding of HA to RHAMM was almost completely blocked by this antibody. These findings suggest that our antibody recognizes RHAMM protein and is useful for blocking HA binding to RHAMM.

Animals↗

Secondary acute monocytic leukemia with a translocation t(8;16)(p11;p13): case report and review of the literature.

Acute myeloblastic leukemia cases carrying the translocation t(8;16) (p11;p13) are characterized by the M4 and M5 subtypes, erythrophagocytosis by the blast cells and a poor prognosis, suggesting a new clinical entity. The t(8;16) fuses the MOZ gene which encodes a histone acetyltransferase, located on 8p11 with the CBP gene which also encodes a histone acetyltransferase, located on 16p13, and recent reports suggested that the chimeric transcription MOZ-CBP is essential for leukemogenesis. A 68-year-old woman who had been treated mainly with paclitaxel and carboplatin for preceding ovarian cancer was admitted to our hospital, complaining of right breast mass. She was diagnosed as having breast cancer and acute monocytic leukemia (M5b). Cytogenetic study with spectral karyotyping analysis revealed the development of 47 XX, + 8, t(8;16)(p11;p13). Eleven cases of therapy-related t(8;16) leukemia including the present case have been reported, but prior treatment with paclitaxel and carboplatin-based chemotherapy has never been reported. The relation of histone acetylase and therapy-related leukemia is discussed.

Aged↗

Diffuse large B-cell lymphoma presenting with hypercalcemia and multiple osteolysis.

Osteolysis and hypercalcemia are observed in 5-15%, and 10%, respectively, of malignant lymphoma patients during their clinical course. However, both osteolysis and hypercalcemia are uncommon at onset of the disease. We encountered a 24-year-old male non-Hodgkin's lymphoma patient who had multiple osteolytic lesion from the onset of the disease and repeated episodes of hypercalcemia during the clinical course. The patient died with refractory disease. We studied the expression of chemokines which might affect bone resorption using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Increased expressions of MIP-1alpha, MIP-1beta and RANKL, which are osteoclast-activating factors, were observed in the RNA derived from the patient's lymphoma cells. The secretion of osteoclast-activating factors such as MIP-1alpha by the tumor cells (and/or bone marrow stromal cells) might be involved in the etiology of osteolysis and hypercalcemia in some malignant lymphoma cases.

Acid Phosphatase↗

Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene.

The present study aimed to characterize the clinical and molecular-cytogenetic features of non-Hodgkin's lymphoma (NHL) with double translocation of the immunoglobulin heavy chain (IGH) gene. G-banding analysis, fluorescence in situ hybridization (FISH) with the IGH (Cgamma and VH) and oncogene (c-MYC, BCL1, BCL2, and BCL6) probes, and long-distance polymerase chain reaction (LD-PCR) were performed on 6 patients with B-cell lymphoma, one with angioimmunoblastic T-cell lymphoma, and one with acute lymphoblastic leukemia (ALL) with B-cell phenotype. G-banding analysis detected two different 14q32 translocations, t(14,18) and add (14)(q32) in a patient with ALL. Two distinct partners of double IGH translocation identified by FISH were as follows: c-MYC + BCL2 in 3 patients, c-MYC + BCL1 in 2, c-MYC + BCL6 in one, BCL2 + 9q22 in one, and 1q21 + 6q27 in one. Colocalization of BCL1 and c-MYC probes was demonstrated in a patient with mantle cell lymphoma. LD-PCR detected c-MYC/Cmu, c-MYC/Calpha and BCL6/Cmu, and c-MYC/Calpha fusion in each one patient. Seven of 8 patients showed high serum LDH. Central nervous system and leukemic involvement was observed in 5 and 6 patients, respectively. Median survival time of patients with c-MYC/IGH translocation was 9 months. The results defined a clinical subset of B-cell lymphoma/leukemia showing extremely poor prognosis. C-MYC/IGH translocation is possibly an evolutionary alteration following the primary IGH translocation with BCL1, BCL2, or BCL6. Furthermore, FISH identified one novel (9q22) and one cryptic chromosomal breakpoints (6q27) involved in IGH translocation.

Adult↗

Usefulness of 67Ga scintigraphy in extranodal malignant lymphoma patients.

OBJECTIVE: 67Ga scintigraphy has a well-documented role in nodal lymphoma for both disease staging and assessment of treatment response. The objective of the present study was to examine the role of 67Ga scintigraphy in diagnosis and assessment of treatment response, in patients with extranodal malignant lymphoma. METHODS: Seventy-one patients with extranodal malignant lymphoma were studied. Whole body scans in all and SPECT scans in some selected patients were performed 72 hours after injection of 67Ga-citrate. The influence of tumor site, histological classification and tumor size on 67Ga scintigraphy sensitivity was analyzed. Twenty-one of the seventy-one patients also had a second 67Ga scintigraphy to assess response to treatment. RESULTS: The overall 67Ga scintigraphy sensitivity was 83.1% (59/71). The sensitivity was low in patients whose extranodal lymphoma occurred in skin (0/3) and urinary bladder (0/1), as compared to other tumor sites. According to the histological classification of the lesion, the sensitivity was lower in low-grade than in intermediate and high-grade lymphoma. According to the tumor size, the sensitivity was low in lesions less than 2 cm in diameter than those more than 2 cm in diameter. The results changed from positive to negative accumulation in 20 (95.2%) of the 21 patients who had 67Ga scintigraphy to assess the response to treatment. These 20 patients showed a good clinical course. CONCLUSIONS: Although 67Ga scintigraphy did not show positive accumulation in patients with skin and urinary bladder lymphoma, it was helpful to confirm the diagnosis and to evaluate the therapeutic effect in most patients with extranodal malignant lymphoma.

Adult↗

High levels of hyaluronan production by a malignant lymphoma cell line with primary effusion lymphoma immunophenotype OHK.

We investigated whether hyaluronan (HA) was produced by a malignant lymphoma cell line with a primary effusion lymphoma immunophenotype, OHK. OHK secreted high levels of HA into the culture supernatant, and reverse transcription polymerase chain reaction showed mRNA for the HA synthases 2 and 3. HA binding protein-reactive HA was present in the plasma membrane and in the cytoplasm. The inoculation of OHK into severe combined immunodeficiency disease mice produced marked viscid ascites with concentrated HA and a vascular-rich mesenteric solid tumour. These results show that HA is produced and secreted by the malignant lymphoma cell line OHK.

Animals↗

Peripheral T-cell lymphoma presenting with rapidly progressing myelofibrosis.

Myelofibrosis following peripheral T-cell lymphoma has rarely been reported. Described here is a case of peripheral T-cell lymphoma with myelofibrosis and elevated transforming growth factor beta (TGF-beta). A 69 years old male was admitted due to anemia and thrombocytopenia. His bone marrow showed fibrosis and was infiltrated with small lymphoid cells and a few residual normal hematopoietic cells. He had presented with hepatosplenomegaly and left inguinal lymph node swelling. Biopsy of the left inguinal lymph node revealed diffuse mature small lymphoid cells with atypical nuclei. Immunophenotyping of the small lymphoid cells were positive for CD3, CD8, TCR alphabeta and HLA-DR and were negative for CD4, CD19, CD20 and CD56. T-cell receptor beta-chain gene was rearranged in bone marrow cells. He was diagnosed as having peripheral T-cell lymphoma complicated with myelofibrosis. Chemotherapy was administrated which improved his pancytopenia and symptoms. Two years later, anemia and thrombocytopenia developed rather quickly, he died because of progression of myelofibrosis with severe pancytopenia.

Aged↗

Increased expression of c-maf in pure red cell aplasia secondary to plasma cell dyscrasia.

Th2 dominancy in the peripheral T helper (Th) cell subsets were reported to be involved in the pathogenesis of pure red cell aplasia (PRCA). We encountered a PRCA case secondary to plasma cell dyscrasia that showed Th2 dominancy at the relapse of PRCA. Increased expression of c-maf, a transcriptional factor which induces Th2 differentiation of naive T-cells, and elevated expression of interleukin (IL)-4 were observed in the RNA derived from patient's bone marrow at relapse of PRCA. Following the administration of methylprednisolone which improved PRCA, normalization of Th1/Th2 ratio and decreased expression of c-maf and IL-4 were observed, which suggests that the upregulation of c-maf might have played a role in the pathogenesis of PRCA secondary to plasma cell dyscrasia.

Aged↗

Aberrant methylation in promoter-associated CpG islands of multiple genes in therapy-related leukemia.

Methylation profile was analyzed in eleven cases of therapy-related leukemia (t-leukemia) for p14, p15, p16, Rb, hMLH1, hMSH2, MGMT, APC, RAR beta, DAPK, RIZ1, FHIT, and SOCS-1 genes by using methylation specific polymerase chain reaction (MSP) analysis. Six (55%) of eleven cases showed methylation of at least one gene. The average time to the development of t-leukemia after the treatment of the primary tumor was significantly shorter in patients with methylation than those without methylation (49.3 months vs. 133.2 months, P=0.044). These results suggest that hypermethylation might be involved in the development of t-leukemia.

Aged↗

Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary effusion lymphoma immunophenotype.

A novel cell line, designated OHK, was established from ascites of a 59-year-old Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large pleomorphic morphology with irregular nuclei and distinct nucleoli, and included immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural examination, rich intermediate filaments, and well-developed Golgi apparati and rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis demonstrated clonal rearrangements of Ig heavy and light chain genes. These observations suggest that OHK cells are derived from preterminally differentiated B cells, and that they have features of PEL. Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid karyotypes with multiple structural abnormalities, and produced some cytokines such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF, interleukin 6 and transforming growth factor beta 1. In particular, vascular endothelial growth factor (VEGF), whose stimulation of vascular permeability is thought to be critical to the pathogenesis of PEL, was also produced in large quantities. These results indicate that OHK may be a useful tool for the investigation of PEL.

Ascitic Fluid↗

Marked thrombocytosis following relapse of acute myeloblastic leukemia associated with development of translocation (2;14) (p13;q32).

Thrombocytosis is a rare finding in acute myeloblastic leukemia (AML). Here, we describe a patient with AML who relapsed with marked thrombocytosis. The patient was initially diagnosed as having AML (M4) with a low platelet count. The patient was started on combination chemotherapy including high-dose etoposide and achieved complete remission. However, the patient relapsed six months later with an extremely high platelet count (72.5 x 10(4)/microl). Cytogenetic analysis at relapse revealed the development of t(2;14)(p13;q32). Despite the repeated combination chemotherapy, the patient died with progressive disease. This case suggests that the additional chromosomal aberration t(2;14)(p13;q32) may be related to abnormal thrombocytosis in AML.

Adult↗

EBV associated hemophagocytic syndrome accompanied by central pontine myelinolysis.

The development of central pontine myelinolysis (CPM) has rarely been reported in association with hemophagocytic syndromes (HPS). Here we report a unique case of Epstein-Barr Virus (EBV)-related HPS which was accompanied with CPM. A 72-year-old man who had no significant medical history was admitted to our hospital due to high fever and progressing dysphasia and dysarthria. Physical examination revealed anisocoria of the right pupil, fixed reaction to light, and paralysis of the left vagus nerves. Magnetic resonance imaging revealed low signal intensity on T1-weighted images and high signal intensity T2-weighted images in the patient's central midpontine lesion. Initial work-up showed anemia and thrombocytopenia with elevated levels of serum ferritin, lactate dehydrogenase, and soluble IL-2 receptor. Bone marrow aspiration revealed hemophagocytosis. The EBV genome was detected in the peripheral blood using the polymerase chain reaction method. He was diagnosed as having EBV-related HPS and CPM. Despite intensive treatment with methylpredonisolone, immunoglobulin, and etoposide, he died due to progressive disease and fungal septicemia. The etiology and relation between CPM and HPS are discussed.

Aged↗

Immunolocalization of peripheral lymph node addressins in normal and neoplastic human thymuses.

Peripheral lymph node addressin is a specific L-selectin ligand of the high endothelial venules that plays an important role in lymphocyte homing to lymph nodes. Tissue selective migration of lymphocytes through this pathway to the thymus has also been proposed. In this work, peripheral lymph node addressin expression was investigated immunohistochemically with a monoclonal antibody, clone MECA-79, in formaldehyde-fixed, paraffin-embedded tissue sections of 5 normal neonatal thymuses, 25 thymomas, 3 thymic carcinomas, and 2 thymic lymphoid hyperplasias. In normal thymuses, peripheral lymph node addressin expression was found in the endothelium of corticomedullary and medullary vessels surrounded by perivascular space. In type B thymomas and thymic lymphoid hyperplasias, peripheral lymph node addressin was detected in the vessels with perivascular spaces, at the medullary differentiation areas, and in paralymphoid follicles, respectively. However, in type A thymomas and thymic carcinomas, MECA-79-positive vessels were restricted to the remnants of pre-existing thymic tissue, and they were absent from the neoplastic areas. These findings suggest that in normal and most neoplastic thymuses, peripheral lymph node addressin is expressed by regions of vascular endothelium corresponding to postcapillary venules that may serve as a pathway for homing of recirculating lymphocytes to the thymus.

Adult↗

[Reversible cardiomyopathy secondary to interferon-alpha in chronic myelogenous leukemia].

Interferon-alpha (IFN-alpha) has been accepted as an effective agent in the treatment of chronic myelogenous leukemias (CML). Cardiac toxicity of IFN-alpha has rarely been reported in cases of CML. A 62-year-old woman with a two-year history of chronic myelogenous leukemia who had been treated with IFN-alpha (10 million U/3 days/week) given subcutaneously with oral hydroxycarbamide 500 mg, presented with chest pain, dyspnea and subconsciousness. Chest X-ray revealed cardiomegaly and congestion, and ultrasonography showed diffuse hypokinesis of the heart with decreased left ventricular ejection fraction (LVEF) 34%. She was diagnosed cardiomyopathy caused by IFN-alpha administration. She was treated with furosemide, dobutamine hydrochloride, milrinone and carperitide. The administration of IFN-alpha was terminated. LVEF was improved to 50% within one month from the onset of events, and the patient was discharged. We discuss herein the cardiomyopathy caused by IFN-alpha in CML.

Cardiomyopathies↗

[Lupus cystitis in the course of Evans syndrome].

A 50-year-old woman with a 4-year history of Evans syndrome was admitted to our hospital because of progressive nausea, appetite loss, body weight loss, diarrhea and abdominal pain. Abdominal ultrasonography revealed pleural effusion, ascites, bilateral hydronephrosis, dilatation of the bilateral ureter, and irregular wall thickness of the urinary bladder. Immunological studies revealed decreased complement components (C3; 72 mg/dl, C4; 7 mg/dl, CH50; 28.8 mg/dl), a x 80 antinuclear antibody titer (homogeneous pattern), antibody against single-stranded DNA 19 U/ml, anti-SS-A antibody over 500 U/ml and negativity for antibody against double-stranded DNA (anti-dsDNA Ab). Although the patient did not fulfill the criteria for systemic lupus erythematosus (SLE), we diagnosed her as having lupus cystitis. Bolus methylprednisolone (mPSL) therapy (1,000 mg mPSL over 3 days, div) was administered, followed by 60 mg PSL, and this led to immediate improvement of the patient's symptoms and laboratory data. Later, anti-dsDNA Ab became positive, and the patient thereby fulfilled the criteria for SLE. Lupus cystitis following Evans syndrome has rarely been reported. The present such case was treated successfully with bolus mPSL therapy.

Anemia, Hemolytic, Autoimmune↗